Method for concentrating raw material solution, and system for concentrating raw material solution

The present invention relates to a concentration method and a concentration system for a feed solution containing water and an organic solvent as a solvent.

Among feed solutions requiring concentration, there are numerous industrial feed solutions containing water and an organic solvent as a solvent. In synthesis processes of substances comprising amino acid sequences such as peptides, enzymes, and proteins (hereinafter referred to as “the peptides”), the solvent in the feed solutions to be concentrated may contain both water and an organic solvent.

The peptides are widely used as diagnostic/test drugs and pharmaceuticals, and the feeds thereof are very expensive. Therefore, when concentrating feed solutions containing peptide, etc., it is important to recover the peptides in high yield without denaturation.

As one method for stably and efficiently concentrating feed solutions containing the peptides, a membrane filtration method using an ultrafiltration membrane is used. Since the membrane filtration method using an ultrafiltration membrane, which is a technique for separating a feed solution by sieving, does not involve a temperature change, it is possible to reduce energy load. In the membrane filtration method using an ultrafiltration membrane, components having a size larger than the cut-off molecular weight of the membrane are retained, but water passes through the membrane. Thus, this method is effective for concentrating the peptides (PTL 1).

A reverse osmosis (RO) method using a membrane which allows a solvent to permeate at a molecular level is known. The RO method is a method for concentrating a feed solution, configured such that the feed solution is pressurized to a predetermined pressure higher than the osmotic pressure of the feed solution and then supplied to an RO membrane module, where only the solvent in the feed solution permeates the RO membrane, thereby removing the solvent (typically water) in the feed solution (PTL 2).

As another concentration method for a feed solution, a forward osmosis (FO) method is known. The FO method is a concentration method for a feed solution, wherein a feed solution is brought into contact with a draw solution having a higher osmotic pressure than the feed solution via a forward osmotic (FO) membrane, and the solvent is diffused from the feed solution to the draw solution. Since the FO method does not require pressurization, it is expected that the solute contained in the feed solution can be efficiently concentrated without adhesion (PTL 3).

As yet another concentration method for a feed solution, membrane distillation (MD) methods are known. As one method of membrane distillation, the DCMD method (Direct Contact MD), in which a feed solution is concentrated by bringing the feed solution into contact with cooling water having a temperature lower than the feed solution and thereby transferring the vapor of the solvent in the feed solution from the feed solution to the cooling water, is well known (PTL 4).

PTL 5 discloses a method in which a forward osmosis method and membrane distillation are combined. In the technique of PTL 5, the membrane distillation method is used to regenerate the draw solution used in the forward osmosis method.

In the membrane filtration method using an ultrafiltration membrane described in PTL 1, since it is necessary to pressurize the feed solution, there is an issue where the adhesion of the solute contained in the feed solution to the membrane surface occurs, reducing the recovery rate. In the case of medium molecular weight drugs being developed these days, where the molecular weight is less than the cut-off molecular weight of the ultrafiltration membrane, the solute partially permeates the ultrafiltration membrane, thus reducing the recovery rate.

In the RO method described in PTL 2, since it is necessary to pressurize the feed solution, there is an issue where the adhesion of the solute contained in the feed solution to the membrane surface occurs, reducing the recovery rate. In the RO method, the osmotic pressure of the solvent (filtered solvent) in the concentrate feed solution does not exceed the pressure of the high-pressure pump used for pressurization, and thus the concentration rate of the feed solution by the RO method is limited by the ability of the pump.

In the forward osmosis process described in PTL 3, since the active layer of the forward osmotic membrane selectively passes water molecules during concentration, there is an issue where a large amount of organic solvent remains in the concentrate when a feed solution containing both water and an organic solvent as a solvent is concentrated.

In the membrane distillation method described in PTL 4, since a component having a low osmotic pressure is preferentially removed out of the system through the membrane, there is an issue where a large amount of water remains in the concentrate when a feed solution containing both water and an organic solvent as a solvent is concentrated. Additionally, when a large amount of water remains in the concentrate, there is an issue where an active component in the feed solution precipitates.

In the technique of PTL 5, the membrane distillation method is used to regenerate the draw solution used for forward osmosis and is not applied to concentrating the feed solution.

An object of the present invention is to provide a concentration method and a concentration system for a feed solution, which are capable of concentrating a feed solution without the conditions of pressurization and heating and capable of controlling the ratio of water and an organic solvent in the feed solution after concentrating to any ratio.

The present invention has been made to achieve the above object.

The present inventors have discovered that when concentrating a feed solution containing water and an organic solvent as a solvent, by combining a concentration method of removing mainly water in the feed solution and a concentration method of removing mainly the organic solvent, the ratio of water and the organic solvent can be adjusted to any ratio, thus arriving at the present invention.

The present invention is described as follows:

<<Aspect 1>> A concentration method for a feed solution containing a solute and a solvent to obtain a concentrate of the feed solution, wherein

<<Aspect 2>> The concentration method for a feed solution according to Aspect 1, wherein the concentration method of removing water and the organic solvent in the feed solution through evaporation is a membrane distillation method.

<<Aspect 3>> The concentration method for a feed solution according to Aspect 1 or 2, wherein the second concentration method is carried out after the first concentration method.

<<Aspect 4>> The concentration method for a feed solution according to Aspect 1 or 2, wherein the first concentration method is carried out after the second concentration method.

<<Aspect 5>> The concentration method for a feed solution according to any one of Aspects 1 to 4, wherein at least one of a solute concentration and a solvent composition in the concentrate of the feed solution is measured online, and execution, change in concentrating rate, or suspension of the first concentration method and the second concentration method is determined in accordance with the measured value.

<<Aspect 6>> The concentration method for a feed solution according to Aspect 5, wherein at least one of the solute concentration and the solvent composition in the concentrate of the feed solution is measured by one or more measuring means selected from the group consisting of specific gravity measurement, pH measurement, conductivity measurement, liquid level measurement, optical rotation measurement, near-infrared spectroscopic analysis, and weight measurement of the concentrate.

<<Aspect 7>> The concentration method for a feed solution according to any one of Aspects 1 to 6, wherein the solvent is a mixture containing

<<Aspect 8>> The concentration method for a feed solution according to any one of Aspects 1 to 7, wherein the solute is one or more selected from the group consisting of an amino acid, a peptide, a protein, a saccharide, a vaccine, a nucleic acid, an antibiotic, an antibody-drug conjugate (ADC), and a vitamin.

<<Aspect 9>> The concentration method for a feed solution according to any one of Aspects 1 to 8, wherein the solute has a number-average molecular weight of 100 to 50,000.

<<Aspect 10>> The concentration method for a feed solution according to any one of Aspects 1 to 9, wherein the temperature of the feed solution is regulated to a range of 1° C. to 50° C.

<<Aspect 11>> The concentration method for a feed solution according to any one of Aspects 1 to 10, wherein an alcohol selected from methanol, ethanol, isopropanol, and t-butanol is used as a solute of a draw solution used in the forward osmosis method.

<<Aspect 12>> The concentration method for a feed solution according to any one of Aspects 1 to 11, wherein

<<Aspect 13>> A concentration system for a feed solution by concentrating a feed solution containing a solute and a solvent to obtain a concentrate of the feed solution, wherein

<<Aspect 14>> The concentration system for a feed solution according to Aspect 13, wherein the concentrating means of removing water and the organic solvent in the feed solution through evaporation is a membrane distillation method.

<<Aspect 15>> The concentration system for a feed solution according to Aspect 13 or 14, wherein the second concentrating means is arranged after the first concentrating means.

<<Aspect 16>> The concentration system for a feed solution according to Aspect 13 or 14, wherein the first concentrating means is arranged after the second concentrating means.

<<Aspect 17>> The concentration system for a feed solution according to any one of Aspects 13 to 16, wherein the system comprises a measuring means of measuring at least one of a solute concentration and a solvent composition in the concentrate of the feed solution online, and operation, change in concentrating rate, or suspension of the first concentrating means and the second concentrating means is determined in accordance with a value measured by the measuring means.

<<Aspect 18>> The concentration system for a feed solution according to Aspect 17, wherein the measuring means of measuring at least one of the solute concentration and the solvent composition in the concentrate of the feed solution is one or more measuring means selected from the group consisting of specific gravity measurement, pH measurement, conductivity measurement, liquid level measurement, optical rotation measurement, near-infrared spectroscopic analysis, and weight measurement of the concentrate.

<<Aspect 19>> The concentration system for a feed solution according to any one of Aspects 13 and 18, wherein the solvent is a mixture containing

<<Aspect 20>> The concentration system for a feed solution according to any one of Aspects 13 to 19, wherein the solute is one or more selected from the group consisting of an amino acid, a peptide, a protein, a saccharide, a vaccine, a nucleic acid, an antibiotic, and a vitamin.

<<Aspect 21>> The concentration system for a feed solution according to any one of Aspects 13 to 20, wherein the solute has a number-average molecular weight of 100 to 50,000.

<<Aspect 22>> The concentration system for a feed solution according to any one of Aspects 13 to 21, wherein the temperature of the feed solution is regulated to a range of 1° C. to 50° C.

<<Aspect 23>> The concentration system for a feed solution according to any one of Aspects 13 to 22, wherein an alcohol selected from methanol, ethanol, and isopropanol is used as a solute of a draw solution used in the forward osmosis method.

<<Aspect 24>> A concentration apparatus for concentrating a feed solution containing a solute and a solvent to obtain a concentrate of the feed solution, wherein

<<Aspect 25>> A concentration apparatus for concentrating a feed solution containing a solute and a solvent to obtain a concentrate of the feed solution, wherein

<<Aspect 26>> The apparatus according to Aspect 24 or 25, wherein at least one of a solute concentration and a solvent composition of the feed solution in the feed solution tank is measured online, and operation, change in concentrating rate, or suspension of the first concentrating unit and the second concentrating unit is automatically determined in accordance with the measured solvent composition.

<<Aspect 27>> The apparatus according to any one of Aspects 24 to 26, wherein

<<Aspect 28>> The apparatus according to any one of Aspects 24 to 26, wherein

According to the concentration method for a feed solution of the present invention, the feed solution can be concentrated without heating and pressurization, and the solvent composition can be adjusted during concentration. Therefore, solvent replacement after the concentrating step is not necessary, and a closed-system apparatus can be configured so that the loss of feed components is small and the concentration treatment can be carried out in a short time.

When the concentration apparatus of the present invention is used, a concentration system for a feed solution having the advantages as described above can be constructed.

<<Concentration System for Feed Solution>>

The concentration system for a feed solution of the present invention is a concentration system for a feed solution by concentrating a feed solution containing a solute and a solvent to obtain a concentrate of the feed solution, wherein